TNF-Dependent Recruitment of the Protein Kinase RIP to the TNF Receptor-1 Signaling Complex
Open accessAbstract
The death domain of tumor necrosis factor (TNF) receptor-1 (TNFR1) triggers distinct signaling pathways leading to apoptosis and NF-kappa B activation through its interaction with the death domain protein TRADD. Here, we show that TRADD interacts strongly with RIP, another death domain protein that was shown previously to associate with Fas antigen. We also show that RIP is a serine-threonine kinase that is recruited by TRADD to TNFR1 in a TNF-dependent process. Overexpression of the intact RIP protein induces both NF-kappa B activation and apoptosis. However, expression of the death domain of RIP Induces apoptosis, but potently inhibits NF-kappa B activation by TNF. These results suggest that distinct domains of RIP participate in the TNF signaling cascades leading to apoptosis and NF-kappa B activation.
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At least in some settings, this reflects major role of RIPK1 in NF-κB activation.
“At least in some settings, this reflects the major role of RIPK1 in NF-κB activation [505–507].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [505]
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- Authors
- Hsu, H., Huang, J., Shu, H.-B., Baichwal, V., & Goeddel, D. V.
- Corresponding author
- Goeddel, David V
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 1996-04
- Volume
- 4
- Issue
- 4
- Pages
- 387-396
- ISSN
- 1074-7613 (ISSN-L)
- OpenAlex
- W2089394364
- Cited by
- 1,182
- References
- 39
- Citations by year
- 2026: 19 · 2025: 17 · 2024: 25 · 2023: 29 · 2022: 35 · 2021: 38 · 2020: 25 · 2019: 38 · 2018: 25 · 2017: 32 · 2016: 27 · 2015: 30 · 2014: 40 · 2013: 35 · 2012: 29
- FWCI
- 35.76
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Rappaport Foundation
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- RIP kinases, TNF receptor 1, TRADD, death domain, TNF signaling, NF-κB activation, apoptosis, serine/threonine kinase, death domain proteins
- MeSH terms
- Amino Acid Sequence, Animals, Cell Line, Humans, Molecular Sequence Data, Proteins, Recombinant Proteins, Tumor Necrosis Factor-alpha, Signal Transduction, NF-kappa B, Apoptosis, Protein Serine-Threonine Kinases, Receptors, Tumor Necrosis Factor, TNF Receptor-Associated Factor 1, Receptor-Interacting Protein Serine-Threonine Kinases
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